I have updated the blog on virus origins quite considerably – new pictures, more detail, more speculation!
Pathways on information flow for RNA viruses
Posts Tagged ‘virus’
Virus Origins II
28 September, 2011HPV vaccines: good, but out of reach for most
28 October, 2010
Human papillomavirus and cervical cancer - copyright Russell Kightley Media
The fact that genital Human papillomaviruses (HPVs) cause cervical cancer in women, as well as a variety of other growths and lesions in both men and women, is not in dispute. The fact that cervical cancer is a major and growing scourge of women in developing countries is also non-contentious: of the more than 500 000 cases and 300 000 deaths due to the disease every year, more than 80% occur in the developing world. This is largely because, unlike their counterparts in the developed world, poor Third World women either do not get screened using the relatively simple cytological detection method known as the Papanicolau (Pap) smear, or do not get treated thereafter. Thus, cervical cancer really is a disease of poverty, given that most deaths occur due to a lack of simple procedures being provided in clinics.
The best method of prevention of an infectious disease is almost always a vaccine: HPV vaccines have been around a while now, and have proved to be both safe and efficacious – both primary requirements of a vaccine. Both Merck and GlaxoSmithKline’s vaccines – the yeast-produced Gardasil and insect cell-produced Cervarix respectively – are virus-like particles (VLPs) composed of the major HPV coat protein L1 only; Cervarix contains particles of the high-risk HPV types (or species) 16 and 18 and Gardasil contains VLPs derived from HPVs 16 and 18 as well as the genital wart-causing 6 and 11.
The vaccines are both “blockbusters” – that is, they both have sales of over US$1 billion – are are possibly the best-researched human vaccines ever made. They are also possibly among the most expensive: Gardasil went on sale in the USA at $120 per dose – and a full treatment consists of 3 doses, for a total cost per person treated of $360; Cervarix retails at around the same price.
This is so far beyond the budget of most people in most countries as to be akin to their expectation of winning a lottery – and of the order of 1000x as expensive as possibly the most widely distributed vaccine in the world, which is Bacillus Calmette-Guerin (BCG), the Mycobacterium tuberculosis vaccine.
It is a sad fact of life that the whole WHO Expanded Programme on Immunisation – EPI – six vaccine bundle of polio, measles, neonatal tetanus, diphtheria, pertussis (whooping cough) and tuberculosis vaccines “… costs no more than US$1 … (at UNICEF-discounted prices), and another US$14 for programme costs (laboratories, transport, the cold chain, personnel and research) to fully immunize a child”. It is also a sad fact that the new generation of vaccines – exemplified by the yeast-made recombinant hepatitis B virus (HBV) subunit vaccine – are expensive even when discounted after patents have expired: thus, HBV vaccine launched at US$150 for three doses in 1986, and came down to around $10 now. It is included in EPI bundles in some countries because of even greater discounting (down to ~$1); however, its cost is generally greater than the rest of the bundle combined.
So what should happen with HPV vaccines? How are they going to get to the people who need them most, at the price they can afford – which is nothing? The simple answer is that governments and international agencies must buy them, as is presently the case with the EPI package – and that they must be very heavily discounted, to allow this.
In fact, at the recent Papillomavirus Conference in July in Montreal (which we should write up in more detail elsewhere), I heard that the Mexican government has managed to secure HPV vaccine at US$27/dose – or 25% of the regular price – for a campaign they are mounting in some regions to supply vaccine for free. So it is possible – however, even this price is far too high, as it represents about the per capita per annum public health expenditure in the poorest countries who probably need it most.
It raises my blood pressure, therefore, when I read that in several highly-developed western countries there are a number of controversies (see also here) around HPV vaccination: yet again, on the heels of the measles and MMR (measles-mumps-rubella viruses) vaccines-cause-autism idiocy, people who can afford vaccines are among the most stupid when it comes to having them.
The facts, as opposed to the hype, are these:
- the vaccines were proven to be safe in extended clinical trials
- they were proven to be efficacious in preventing infection and development of precancerous lesions and genital warts – in men as well as in women
Inflammatory stories about deaths due to HPV vaccines are just that – stories. A recent publication from India, where the government suspended a vaccine study due to deaths of girls involved in the trial, puts things into perspective:
“The causes of death had been scrutinized by the State Government and reported to ICMR and Drugs Controller General of India; all were satisfied that no death was vaccine-related [ my emphasis]. We understand that there is an unusually high frequency of death among girls in this community, which is what deserves immediate enquiry and remedial interventions….
The death of a 14-year old British girl shortly after receiving HPV Vaccine,evoked considerable media attention across the world. The necropsy studies showed that she had malignant tumor affecting her heart and lungs…. The vaccine was not her cause of death.”
There is also considerable silliness surrounding the vaccination of girls – and, hopefully, boys! – against what is very largely a sexually transmitted virus.
Do people have the same problem with HBV?
Or – is it possible?? – they don’t know that it is also frequently a sexually-transmitted disease, among adults at least?
In any case, the kinds of prudishness-by-proxy that result in non-vaccination against HPV or HBV are simple foolishness.
And I would be happy to tell anyone so.
Meantime, we want to make HPV vaccines in plants. Any sponsors??
They DO get everywhere, don’t they?
21 October, 2010
Euglena cells in pondwater. Image copyright Russell Kightley, http://www.rkm.com.au
Thanks to AJ Cann’s MicrobiologyBytes, and The Scientist:
Decoding the Genome of Chlorella Microalgae, a Promising Genus for Biofuel Production
ScienceDaily (Oct. 13, 2010)
“…the analysis of the Chlorella genome has also revealed numerous genes governing the synthesis of flagellar proteins, which suggests that this species could have a sexual cycle that has gone unnoticed until now. Last but not least, the ability of Chlorella algae to synthesize chitin could have been inherited from a virus (itself endowed with chitinase activity) having secured exclusive use of its host against other viruses incapable of piercing through its protective shell. This “monopoly” scenario illustrates a new mode of co-evolution between viruses and their hosts.”
Gotta love ’em – because maybe we and many other things couldn’t be here without ’em. This builds on previous evidence that retroviruses probably helped in the evolution of placental mammals, that much of the planet’s oxygen may be due to viruses, and that viruses often aid hosts in developing resistance against them.
However, the parent paper is always preferable to a commentary – and I am indebted to Guillaume Blanc – the corresponding author – for a copy of the paper; our otherwise reliable library service fell down on access to the Plant Cell! This allows me to quote the following (bold text my emphases):
The Chlorella variabilis NC64A Genome Reveals Adaptation to Photosymbiosis, Coevolution with Viruses, and Cryptic Sex
Guillaume Blanc et al., Plant Cell Advance Online Publication
Published on September 17, 2010; 10.1105/tpc.110.076406
With 233 predicted enzymes involved in carbohydrate metabolism, NC64A appears much better equipped for synthesizing and modifying polysaccharides than the other sequenced chlorophytes that have between 92 (O. tauri) and 168 (C. reinhardtii) of such predicted enzymes…. However, we did not find homologs of the Arabidopsis proteins involved in the synthesis of cellulose (cellulose synthase CesA) or hemicellulose (hemicellulose syn- thase CLS), the major components of the primary cell wall of land plants. Instead, experimental evidence suggests that the cell wall of Chlorella species, including NC64A, contain glucosamine polymers such as chitin and chitosan….
Chitin is a natural component of fungal cell walls and of the exoskeleton of arthropods but is not normally present in green algae. The origin of chitin and its derivatives in the Chlorella genus has long been an enigma. Except for the plant-type chitinase gene, which is found in land plants (but not in chlorophytes apart from Chlorella), the four gene classes involved in forming and remodeling chitin cell walls (i.e., chitin synthase, chitin deacetylase, chitinase, and chitosanase) are absent in all the other fully sequenced Viridiplantae species. By contrast, homologs for each of these families exist in genomes of Chlorella viruses. The viral genes are presumably involved in degradation of the Chlorella cell wall (chitinase and chitosanase)… and production of chitinous fibers on the external surface of virus-infected cells (chitin synthase and chitin deacetylase) …. Phylogenetic analysis suggests that the Chlorella ancestor exchanged the bacterial-type chitinase and chitin-deacetylase genes with the chloroviruses.
And as I have often said (well, mostly to myself, but also in MicrobiologyBytes) – “Profound Insight (No. 4): in order to understand viruses, we should all be working on seawater…. That is where the diversity is, after all; that is where the gene pool that gave rise to all viruses came from originally – and who knows what else is being cooked up down there?”.
Amen. But let’s add ponds to that.
On the utility of Pink Floyd’s “The Grand Vizier’s Garden Party” as a metaphor for virus multiplication
16 September, 2010
…which pretty much explains the concept…what’s that? Why? Well, because the above-mentioned song – off the very strange and very wonderful album Ummagumma, released in 1969 – incorporates three subsections.
From the tracklisting:
“The Grand Vizier’s Garden Party” (N Mason) – 8:44
- Part 1: “Entrance” – 1:00
- Part 2: “Entertainment” – 7:06
- Part 3: “Exit” – 0:38
All clear now? No? Ah, well, you need to consult the relevant parts of the Web material, don’t you? Which would be here, and here…and of course, we never got around to exit as such, so you may as well look here instead.
Which just goes to show that, however hard one tries, it is close to impossible to update a whole set of Web pages AND keep all the links current! Ah, well – that’s an aspect of electronic teaching with its own comment, right here.
But I digress: “metaphor”, I said. Something like a “simile”, only different, as I’ve heard it described. And another digression, to cartoon country this time – which shows how we virologists normally treat metaphors and their filthy ilk.
And is it a good metaphor, you ask? Well, yes – for one reason, because
- first, students still know who Pink Floyd is/are, so they remember it better;
- second, because it is a very simple encapsulation of the process;
- third, because it neatly separates three crucial aspects of the virus life cycle –
- and fourth, it gives you the opportunity to describe three very different kinds of strategy for messing with said life cycle.
And thinking of 4, and just of HIV for example, those would be:
- entry inhibitors, like antibodies or fusion inhibitors
- nucleoside analogue or non-nucleoside reverse transcriptase inhibitors, and
- protease inhibitors to prevent polyprotein processing.
And I’ve been doing it for 25 years, and see no reason why I should stop using it now. Or stop playing “Another Brick in the Wall” when I put up long definitions. Or stop mentioning that Pink Floyd have the second-longest song title of which I am aware. Or that Hoagy Carmichael* has the longest….
Enough said, probably. Just to say that it helps make virology fun. At least for me B-)
* = I’m a Cranky Old Yank in a Clanky Old Tank on the Streets of Yokohama with my Honolulu Mama Doin’ Those Beat-o, Beat-o Flat-On-My-Seat-o, Hirohito Blues
Dear New Scientist
6 June, 2010In the full expectation that my letter will not see the light of day – nothing I have ever written to NS over some 15 years ever has – I will put this here, where more some people may see it.
Dear Editor:
I recall being a little miffed when I read the original article on
biodiversity in NS (24 April) – because there was no mention at
all of the greatest part of the biodiversity on this (and probably any
other) planet, which is viruses. There are more viruses on Earth than
any other kinds of organisms, and virus genomes provide the greatest
source of gene diversity – yet they don’t rate a mention.
And then, in your Letters page of the 22 May issue, people take up
cudgels on behalf of fungi, of all things!
Cellism, that’s all it is….
Rift valley fever: a problem – and a solution?
17 March, 2010
Rift valley fever virions: Linda Stannard, UCT
It was an interesting week, what with a Rift valley fever virus (RVFV) outbreak in South Africa associated with two human deaths – and an excellent journal club presentation (thanks, Liezl!) on a new candidate virus-like particle vaccine made in insect cells. RFV was in fact worked on in the 1960s at UCT in the old Virus Research Unit under the legendary Dr Alfred Polson at the then Medical School (see pictures link here) – and a couple of folk even got infected while trying to purify it, but we won’t speak of that.
First, the news:
Health-e (Cape Town)
South Africa: Rift Valley Fever Update – a Total of 21 Cases Have Been Confirmed
15 March 2010 press release
The following is a statement by [South African] Deputy Minister of Health Dr Molefi Sefularo, MP, pertaining to the recent deaths from Rift Valley Fever in South Africa.
As of 15 March 2010, a total of 21 human laboratory confirmed cases of River [sic] Valley Fever (RVF) have been confirmed – all acquired in Free State – with two deaths. This brings a total to 22 human cases of RVF – with one in Northern Cape.
Most of these cases reported direct contact with RVF-infected livestock and or linked to farms with confirmed animal cases of RVF. The human cases are; farmers, veterinarians and farm workers. Additional suspect cases are currently being tested.
…
While there is no specific treatment, the majority of persons affected will recover completely. People should avoid contact with the tissues of infected animals, refrain from drinking unpasteurised milk and prevent mosquito bites to avoid becoming infected. Farmers and veterinarians should wear protective clothing when handling sick animals or their tissues. There is no routine vaccine available for humans.…
Rift Valley Fever (RVF) is a viral disease that can cause severe disease in a low proportion of infected humans.The virus is transmitted by mosquitoes and causes outbreaks of abortion and deaths of young livestock (sheep, goats and cattle). Humans become infected from contact with infected tissues of livestock and less frequently from mosquito bites. In sub-Saharan Africa the mosquitoes which transmit the virus do not enter human dwellings but feed on livestock outdoors at night. The disease occurs throughout Africa and Madagascar when exceptionally heavy rains favour the breeding of the mosquito vectors.
Clinical features in humans
Typically illness is asymptomatic or mild in the vast majority of infected persons, and severe disease would be expected to occur in less than 1% of infected persons.
Key symptoms:
The incubation period (interval from infection to onset of symptoms) for RVF varies from two to six days.
- Sudden onset of flu-like fever and/or muscle pain.
- Some patients develop neck stiffness, sensitivity to light, loss of appetite and vomiting.
Symptoms of RVF usually last from four to seven days, after which time the immune response becomes detectable with the appearance of antibodies and the virus gradually disappears from the blood.
Severe form of RVF in humans includes:
- Vision disturbances
- Intense headache, loss of memory, hallucinations, confusion, disorientation, vertigo, convulsions, lethargy and coma and;
- Haemorrhagic Fever [rarely – Ed.]
The public living in the affected areas is encouraged to seek medical attention at their nearest Health facilities, should they have any of the above symptoms.
This is an unusual outbreak, because these normally occur only in high summer rainfall regions near the tropics, on the African east coast – and not far inland in essentially arid distinctly sub-tropical areas, like the Free State and Northern Cape.
However, there is news at hand that may be of use in the future: while there is currently no human vaccine, and veterinary vaccines are apparently so attenuated as to require several applications to be effective, SM de Boer and colleagues in The Netherlands claim that subunit VLP vaccines derived by envelope glycoprotein expression in insect cells appear to confer complete protection in vaccinated animals.
Vaccine. 2010 Mar 8;28(11):2330-9. Epub 2010 Jan 5.
Rift Valley fever virus subunit vaccines confer complete protection against a lethal virus challenge.
de Boer SM, Kortekaas J, Antonis AF, Kant J, van Oploo JL, Rottier PJ, Moormann RJ, Bosch BJ.
“Here we report the evaluation of two vaccine candidates based on the viral Gn and Gc envelope glycoproteins, both produced in a Drosophila insect cell expression system. Virus-like particles (VLPs) were generated by merely expressing the Gn and Gc glycoproteins. In addition, a soluble form of the Gn ectodomain was expressed and affinity-purified from the insect cell culture supernatant. Both vaccine candidates fully protected mice from a lethal challenge with RVFV. Importantly, absence of the nucleocapsid protein in either vaccine candidate facilitates the differentiation between infected and vaccinated animals using a commercial recombinant nucleocapsid protein-based indirect ELISA”.
Great accomplishments; great paper – and I note that if you can do it in insect cells, you can do it in plants…just like influenza viruses.
Because, as de Boer et al. state in their Introduction:
“Although the overall case-fatality rate is estimated at 0.5–1.0%, recent outbreaks show considerably higher numbers. The high case-fatality rates combined with the potential of rapid spread via its vector explains the recognition of RVFV as a potential bioterrorism agent by the United States government. Given the impact of RVF outbreaks on livestock, the human population, and the economy, there is an urgent need for a safe and effective vaccine.” [my emphases]
And one backed by the US Government – which used to work on it as a bioterror agent, according to Wikipedia. Ah, well: some day they’ll just want to do it because it’s the humanitarian thing to do. Like now, possibly: DARPA is funding Fraunhofer USA to the tune of $4.4 million to make H1N1 vaccines in plants, following their successes over the last couple of years in especially transiently expressing HA proteins.
Going green: the sensible thing to do.
Zambia fever virus: latest
8 October, 2008Latest links:
“120 people under observation for killer virus” SABC, October 8th
“Killer-fever link found by luck ” Independent On-Line 08-10-08
And just as a reminder that life goes on: a Congo fever patient from here in South Africa.
Painting With Viruses
21 May, 2008Suhail Rafudeen should be a virologist…B-) Here’s another piece of treasure from his Web trawling:
Public release date: 20-May-2008
Federation of American Societies for Experimental Biology
Scientists ‘paint’ viruses to track their fate in the body New study in the FASEB Journal describes a molecular ‘painting’ method to colors the culprit
Bethesda, MD-Biologists from Austria and Singapore developed a technique that adds a new twist on the relationship between biology and art. In an article recently published online in The FASEB Journal (http://www.fasebj.org) and scheduled for the August 2008 print issue, these researchers describe how they were able to coat-or paint-viruses with proteins. This breakthrough should give a much-needed boost to the efficiency of some forms of gene therapy, help track and treat viral disease and evolution, improve the efficiency of vaccines, and ultimately allow health care professionals track the movement of viral infections within the body. Specifically, the new method should make it easier to track and treat infectious diseases such as HIV/AIDS, influenza, hepatitis C, and dengue fever. And because viruses can also be used to introduce biotechnology drugs and replacement genes, and act as vaccines, this research should lead to new treatments for cancer, cardiovascular, metabolic and inherited disorders.
“This technology should provide a new tool for the treatment of many diseases,” said Brian Salmons, one of scientists who co-authored the study. “Even if you are working with a virus that is unknown or poorly characterized, it is still possible to modify or paint it. This is very interesting for emerging diseases.”
In the article, Salmons and colleagues explain how they mixed purified proteins (glycosylphophatidylinositol anchor proteins) with lipid membranes to make it possible to bind these proteins to the outer “skin” (the lipid envelope) of viruses. Even with the new paint job, the viruses remained infectious. While the experiment only involved one type of protein and two types of viral vectors, Salmons says the technique could be expanded and used to apply “paint” made up of other proteins, dyes, and a variety of unique markers.
“Biology and art converge daily: people paint their nails, color their hair, and tattoo their skin,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Now this convergence has entered a new dimension as painted viruses permit scientists to track, cure and prevent disease.”
I think Dr Weissman may have an exciting life outside of science…B-) But seriously, this is a VERY useful development: keeping viruses infectious while being able to track them, even in real time, and show where different viruses infecting the same cells end up…the possibilities expand as you think of them.
Truly little nanomachines, viruses: and now you can specify the colour.
What Rough Beast
19 May, 2008I was surprised and rather gratified to see – via a suitably modest no-commentary post in MicrobiologyBytes – that ViroBlogy has been noticed by none other than the June editorial of Nature Reviews Microbiology.
Along with rather more material on MicrobiologyBytes and Small Things Considered. But hey, a review’s a review…!
There are a number of useful comments and other links in the blog version of the post, on how to actually interact with such material, and the potential of “Web 2.0” applications.
So get busy, students…the wiki is coming – in fact, it was already established, but will be re-invented before the second semester – and your participation is vital.
Oxygen from viruses??
7 April, 2008I thank my colleague Suhail Rafudeen for alerting me to this:
“Some Of Our Oxygen Is Produced By Viruses Infecting Micro-organisms In The Oceans
ScienceDaily (Apr. 6, 2008) – Some of the oxygen we breathe today is being produced because of viruses infecting micro-organisms in the world’s oceans, scientists heard April 2, 2008 at the Society for General Microbiology’s 162nd meeting.
About half the world’s oxygen is being produced by tiny photosynthesising creatures called phytoplankton in the major oceans. These organisms are also responsible for removing carbon dioxide from our atmosphere and locking it away in their bodies, which sink to the bottom of the ocean when they die, removing it forever and limiting global warming.
“In major parts of the oceans, the micro-organisms responsible for providing oxygen and locking away carbon dioxide are actually single celled bacteria called cyanobacteria,” says Professor Nicholas Mann of the University of Warwick. “These organisms, which are so important for making our planet inhabitable, are attacked and infected by a range of different types of viruses.”
The researchers have identified the genetic codes of these viruses using molecular techniques and discovered that some of them are responsible for providing the genetic material that codes for key components of photosynthesis machinery.
“It is beginning to become to clear to us that at least a proportion of the oxygen we breathe is a by-product of the bacteria suffering from a virus infection,” says Professor Mann. “Instead of being viewed solely as evolutionary bad guys, causing diseases, viruses appear to be of central importance in the planetary process. In fact they may be essential to our survival.”
Viruses may also help to spread useful genes for photosynthesis from one strain of bacteria to another.
Adapted from materials provided by Society for General Microbiology, via EurekAlert!, a service of AAAS”
Fascinating concept: viruses as an essential link in the circle of life?! Not so far-fetched, though: just because we know them largely because of their propensity to cause, and our fascination with, diseases that affect us and our livestock and crops…doesn’t mean that is all there is.
Viruses have been around as long as any other form of life, and it would be strange indeed if some form(s) of commensalism and/or symbiosis had not evolved.
…and see here for some fascinating speculations on the possible involvement of viruses with the origin of eukaryotes.
ViroBlogy 
